DESCRIPTION: (Adapted from Applicant's application) The long term goal of this project is to further elucidate factors that influence engraftment of allogeneic CD34+ hematopoietic stem and progenitor cells (HP/SC) in utero. Postnatal allogeneic bone marrow transplants can cure many heritable diseases that affect HP/SC and lymphohematopoietic progeny. However, this form of therapy requires supralethal doses of radio/chemo therapy and post-transplant immunosuppression to ensure engraftment and prevent graft verses host disease (GVHD). Effective postnatal therapy is also limited by the availability of a suitably HLA matched donor and, if there is an available donor, transplantation is frequently done only after the onset of clinical symptoms. Unfortunately, many disorders produce irreversible organ damage early in life. In utero transplantation of allogeneic HP/SC has the potential to avoid the morbidity and mortality of postnatal therapy. Experiments of nature and experimental animal models suggest that in utero transplantation should be feasible. Successful engraftment of CD34+ and HP/SC from fetal liver cells has been reported in fetuses with immune deficiencies. Unfortunately, it is unclear if in utero transplantation of immunologically normal fetuses will result in clinically relevant levels of chimerism. Appropriate animal models are needed to determine the role of HLA, cell type and quantity as well as of hematopoietic space. In fetal non-human primates immunologic and hematologic development is similar to that of the human fetus, suggesting that they should be an appropriate animal model in which to evaluate factors that may improve competitive engraftment of hematopoietic stem cells in utero.